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Titolo:
Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas maltophilia L1 metallo-beta-lactamase
Autore:
Spencer, J; Clarke, AR; Walsh, TR;
Indirizzi:
Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, Bristol BS8 1TD, Avon,England Univ Bristol Bristol Avon England BS8 1TD , Bristol BS8 1TD, Avon,England Univ Bristol, Sch Med Sci, Dept Biochem, Bristol BS8 1TD, Avon, England Univ Bristol Bristol Avon England BS8 1TD Bristol BS8 1TD, Avon, England
Titolo Testata:
JOURNAL OF BIOLOGICAL CHEMISTRY
fascicolo: 36, volume: 276, anno: 2001,
pagine: 33638 - 33644
SICI:
0021-9258(20010907)276:36<33638:NMOHOT>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
TIGHT-BINDING INHIBITOR; BACTEROIDES-FRAGILIS; XANTHOMONAS-MALTOPHILIA; CRYSTAL-STRUCTURE; AEROMONAS-HYDROPHILA; SEQUENCE-ANALYSIS; GENE BLA(IMP); DERIVATIVES; CATALYSIS; SUBSTRATE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Spencer, J Univ Bristol, Sch Med Sci, Dept Pathol & Microbiol, Univ Walk, Bristol BS81TD, Avon, England Univ Bristol Univ Walk Bristol Avon England BS8 1TD on, England
Citazione:
J. Spencer et al., "Novel mechanism of hydrolysis of therapeutic beta-lactams by Stenotrophomonas maltophilia L1 metallo-beta-lactamase", J BIOL CHEM, 276(36), 2001, pp. 33638-33644

Abstract

Stopped-flow tryptophan fluorescence under single turnover and pseudo-first-order conditions has been used to investigate the kinetic mechanism of beta -lactam hydrolysis by the Stenotrophomonas maltophilia L1 metallo-beta -lactamase. For the cephalosporin substrates nitrocefin and cefaclor and thecarbapenem meropenem, a substantial quench of fluorescence is observed on association of substrate with enzyme. We have assigned this to a rearrangement event subsequent to formation of an initial collision complex. For the colorimetric compound nitrocefin, decay of this dark intermediate represents the overall rate-determining step for the reaction and is equivalent to decay of a previously observed state in which the beta -lactam amide bond has already been cleaved. For both cefaclor and meropenem, the rate-determining step for hydrolysis is loss of a second, less quenched state, in which, however, the beta -lactam amide bond remains intact. We suggest, therefore,that the mechanism of hydrolysis of nitrocefin by binuclear metallo-beta -lactamases may be atypical and that cleavage of the-lactam amide bond is the rate-determining step for breakdown of the majority of beta -lactam substrates by the L1 enzyme.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/05/20 alle ore 15:21:12